Is GPC3 p.Val119Phe (c.355G>T) pathogenic?

GPC3 p.Val119Phe (c.355G>T) is classified Uncertain significance in GPC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-10). AlphaMissense: likely pathogenic (0.7955); Ultra-rare (popmax 0.0606%, amr); Associated with Inborn genetic diseases.

What condition is associated with GPC3 p.Val119Phe (c.355G>T)?

GPC3 p.Val119Phe (c.355G>T) is associated with Inborn genetic diseases, Wilms tumor 1, Simpson-Golabi-Behmel syndrome type 1 (ClinVar).

How common is GPC3 p.Val119Phe (c.355G>T) in the general population?

GPC3 p.Val119Phe (c.355G>T) is ultra-rare (popmax 0.0606%, amr) (gnomAD).

What do computational predictors say about GPC3 p.Val119Phe (c.355G>T)?

AlphaMissense predicts likely pathogenic (score 0.7955) — an in-silico prediction, not a clinical call.

GPC3 p.Val119Phe

c.355G>T · rs1060502171 · VCV408889

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0606%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7955	likely pathogenic
REVEL	0.272	benign-leaning
SaProt	LLR -10.47	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 449 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0606% Admixed American · 23/37,932 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0351%

Overall 0.0219% 223/1,020,147 alleles · ultra-rare exomes 221/930,592 · genomes 2/89,555 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0606%	1,649
South Asian	0.056%	1,787
East Asian	0.0527%	1,898
Ashkenazi Jewishnot grpmax-eligible	0.036%	2,777
Remaining individualsnot grpmax-eligible	0.0293%	3,414
African / African-American	0.0261%	3,839
European (non-Finnish)	0.0166%	6,008
Finnishnot grpmax-eligible	0.00728%	13,729

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GPC3
Protein: p.Val119Phe
Coding: c.355G>T
MANE Select: NM_004484
dbSNP: rs1060502171
Type: single nucleotide variant
Location: chrX:133754159 (GRCh38)
Structure: AlphaFold pLDDT 75.60 · 4 PDB
Residue 119: an α-helix

Full GPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Wilms tumor 1 Simpson-Golabi-Behmel syndrome type 1

Similar variants

GPC3 p.Val119del Uncertain significance ★ same residue
GPC3 c.337+2T>A Likely pathogenic ★★ same condition
GPC3 p.Arg199Ter Pathogenic ★★ same condition
GPC3 p.Arg254Ter Pathogenic ★★ same condition
GPC3 p.Arg387Ter Pathogenic ★★ same condition
GPC3 p.Arg86Ter Pathogenic ★★ same condition
GPC3 p.Glu298Ter Pathogenic ★★ same condition
GPC3 p.Gly556Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gpc3-p-val119phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown